喷昔洛韦眼用温度敏感原位凝胶的制备及评价（英文）

目的研制以普朗尼克F127为主要基质的喷昔洛韦制剂,以提高其眼部生物利用度。方法通过将HPMC K4M或卡波姆934P与普朗尼克F127复合使用,制备了喷昔洛韦的温度敏感原位凝胶。以胶凝温度、流变学、药物释放特性、药代动力学及眼部刺激性等为指标进行筛选,得到最优化处方。结果使用HPMC K4M或者卡波姆934P均能降低凝胶的胶凝温度,略微增加其粘度,延缓体系中药物的释放速率;药物释放为非Fick扩散;所有处方均未表现出眼部刺激或对角膜的损伤;含卡波姆934P和普朗尼克F127的凝胶体系的眼部生物利用度最高。结论含普朗尼克F127的喷昔洛韦制剂能够以滴眼液的形式给药,而达到眼部温度时可形成凝胶;体内外评价结果表明,含有HPMC K4M或卡波姆934P以及低浓度普朗尼克F127（12%）的喷昔洛韦制剂,提高了药物在眼部的生物利用度,是一种很有前景的眼部给药系统。

Preparation and evaluation of ophthalmic thermosensitive in situ gels of penciclovir

Aim To develop pluronic F127(PF127)based formulations of penciclovir(PCV)aimed at enhancing its ocular bioavailability.Methods Thermosensitive in situ gels of penciclovir were prepared through combination of HPMC K4M or carbopol 934P and pluronic F127.Optimized formulations were examined through measuring gelation temperature,rheology speciality,drug release behavior,pharmacokinetics and ocular irritation.Results The gelation temperature was reduced by adding HPMC K4M or carbopol 934P,and the viscosity was enhanced slightly.Either HPMC K4M or carbopol 934P delayed the release of PCV from in situ gel.PCV was released by non-Fickian diffusion.The study of ocular irritation for different PCV formulations did not show any irritation or damage for the cornea.PCV bioavailability from combination of carbopol 934P and pluronic F127 gels was higher than that obtained from any other gels.Conclusion Pluronic F127 formulations of PCV can be used as liquid for administration by instilling into the eye.Facilitated by the appropriate eye temperature,the formulations were transformed to gel phase.On the basis of in vitro and in vivo results,PCV formulations containing HPMC K4M or carbopol 934P and low concentra-tion of pluronic F127(12%)showed potential for use as a drug delivery system with improved ocular bioavailability.